Antiepileptics

Question 1

Phenytoin

Answer 1

• Voltage-gated Na channel stabilizer: stabilize inactive conformation of Na channel
• Seizures: less effective for absence, myoclonic, atonic
• Side effects: Rash, gingival hyperplasia, hirsutism, lupus-like reaction; can cause contraceptive failure, Mild myelosuppression, increased LFT; long-term: cerebellar degeneration, peripheral neuropathy, osteoporosis
• IV infusion limited by hypotension; hepatic enzyme inducer (both auto- and hetero-inducer), highly protein bound

Question 2

Carbamazepine

Answer 2

• Voltage-gated Na channel stabilizer: stabilize inactive conformation of Na channel
• Seizures: complex partial, bipolar, neuropathic pain
• Side effects: Rash (rarely, Stevens-Johnson), mild myelosuppression, mild increase in LFTs; can cause contraceptive failure
• Hepatic enzyme inducer (both auto- and hetero-inducer); highly protein bound; must increase dose in 1-2 wks due to autoinduction; side effects likely due to epoxide metabolite

Question 3

Oxcarbamazepine

Answer 3

• Voltage-gated Na channel stabilizer: stabilizer inactive conformation of Na channel
• Complex partial, bipolar, neuropathic pain
• Side efffects: Rash (rarely, Stevens-Johnson), mild myelosuppression, mild increase in LFTs; can cause contraceptive failure
• Designed to bypass carbamazepine epoxide; less protein-bound, less autoinduction, fewer interactions, less toxic, longer half-life than carbamazepine

Question 4

Lamotrigine

Answer 4

• Voltage-gated Na channel stabilizer: stabilize inactive conformation of Na channel
• Primary generalized epilepsies, absence seizures; indicated in children; bipolar disorder; neuropathic pain
• Side effects: Rash, (rarely, Stevens-Johnson): slow initial titration important; may lead to contraceptive failure
• May exacerbate myoclonic seizures; competes with valproic acid for excretion (potential synergy); hepatic enzyme inducer; not very protein bound

Question 5

Valproate (Depakote)

Answer 5

• Likely affects Na-gated channels and GABA system
• Broad spectrum: absence, myoclonic, tonic-clonic, primary generalized, partial onset, and secondary generalized seizures (but not absence seizures); IV for status epilepticus; bipolar treatment, migraine and long-term cluster headache prophylaxis
• Side effects: Weight gain, hair turnover, hyperammonemia (which can be mitigated with oral carnitine), teratogenicity, blood dyscrasias, pancreatitis

Question 6

Vigabatrin

Answer 6

• GABAergic antiepileptic: GABA transaminase binder–slows down intracellular breakdown of GABA
• Anti-epileptic
• Works on GABA-A

Question 7

Tigabine

Answer 7

• GABAergic antiepileptic: GABA reuptake inhibitor
• Antiepileptic
• Works on GABA-A

Question 8

Benzodiazapines

Answer 8

• GABAergic antiepileptic: bind GABA-A
• Status epilepticus
• Sedation
• Tolerance develops

Question 9

Gabapentin

Answer 9

• GABA analog: block presynaptic influx of Ca
• Adjunct for partial complex epilepsy; more commonly used for neuropathic pain
• Sedation
• Absorption limited by intestinal AA transporter (there is a Tm); limited protein binding; no metabolism or drug interaction in humans (so few side effects)

Question 10

Pregabalin

Answer 10

• GABA analog: block presynaptic influx of Ca

- Adjunct for partial complex seizures, commonly used for neuropathic pain

Question 11

Topiramate

Answer 11

• Glutamate receptor blocker: Partial AMPA, Kainate Ca receptor blocker; secondary effect at voltage-gated Na channel, GABA system
• Partial onset seizures, secondary generalized seizures, primary generalized epilepsy; migraine prevention, long-term prevention of cluster headaches
• Mild metabolic acidosis, kidney stones (due to some carbonic anhydrase activity); modest weight loss; rare acute glaucoma; sedation
• Word finding problems
• Carbonic anhydrase activity leads to mild metabolic acidosis, which leads to respiratory compensation, which leads to mild alkalosis, which leads to calcium ionization, which leads to tingling; treat with vitamin C (acidify urine)

Question 12

Felbamate

Answer 12

• Glutamate receptor blocker: NMDA receptor blocker; secondary effect at voltage-gated Na and Ca channels, GABA system
• Partial onset seizures with or without secondary generalization; medically refractory epilepsy
• Uncommon but potentially fatal. Aplastic anemia, acute hepatic failure. Requires monitoring.

Question 13

Levetiracetam (Keppra)

Answer 13

• Synaptic vesicle binder: binds synaptic vesicle protein 2, less NT release
• Partial onset seizures, secondary generalized seizures; maybe primary generalized epilepsy
• Well tolerated; sedation, mostly; rarely, irritability, aphasia, thrombocytopenia

Question 14

Ethosuximide

Answer 14

• Voltage-gated Ca channel blocker: blocks T type Ca channels in thalamo-cortical circuits
• Absence seizures only, neuropathic pain
• Side effects: nausea, sedation, irritability